Olcegepant-BIBN-4096-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOlcegepantCat. No.: HY-10095CAS No.: 204697-65-4Synonyms: BIBN-4096; BIBN 4096BS分式: CHBrNO分量: 869.65作靶点: CGRP Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶

2、解性数据体外实验 DMSO : 50 mg/mL (57.49 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.87 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (2.87 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Olcegepant是有效和选择性的降钙素基因相关

3、肽1 (CGRP1) 受体 拮抗剂，IC50 和 Ki 分别为0.03 nM，14.4pM。IC50 & Target IC50: 0.03 nM (CGRP1) 1Ki: 14.4 pM (hCGRP) 2体外研究 Olcegepant possesses higher affinity for the human CGRP receptor than the endogenous ligand CGRP and150-fold higher affinity compared to the peptidic antagonist CGRP8-37. Olcegepant reverses

4、CGRP-mediated vasodilation in human cerebral vessels and inhibits neurogenic vasodilation in a surrogate animalmodel of migraine pathophysiology 1. Olcegepant (BIBN4096BS) is extremely potent at primate CGRPreceptors exhibiting an affinity (Ki) for human CGRP receptors of 14.46.3 (n=4) pM 2. Several

5、 lines ofevidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novelabortive migraine treatment. Olcegepant (BIBN4096BS) exhibits competitive antagonism at the CGRPreceptor present in SK-N-MC cells. Isolated human cerebral, coronary, and omental arteries a

6、re studied witha sensitive myograph technique. CGRP induces a concentration-dependent relaxation that is antagonized byOlcegepant in a competitive manner 3.体内研究 Olcegepant (BIBN4096BS) in doses between 1 and 30 g/kg (i.v.) inhibits the effects of CGRP, released bystimulation of the trigeminal gangli

7、on, on facial blood flow in marmoset monkeys 2. Pre-treatment withOlcegepant (900 g/kg) inhibits the capsaicin-induced expression of Fos throughout the spinal trigeminalnucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in thetrigeminal ganglion is no

8、t changed by Olcegepant pre-treatment 4. Olcegepant (0.3 to 0.9 mg/kg, i.v.)markedly reduces mechanical allodynia in CCI-ION rats. Olcegepant (0.6 mg/kg, i.v.) significantly reducesthe number of c-Fos immunolabeled cells in spinal nucleus of the trigeminal nerve and upregulation of ATF3transcript (a

9、 marker of neuron injury) but not that of interleukin-6 in trigeminal ganglion of CCI-ION rats 5.PROTOCOLKinase Assay 2 125I-hCGRP is used as the radioligand. The incubation buffer contained (in mM): Tris 50, NaCl 150, MgCl25and EDTA 1, (ethylene diamine tetra-acetic acid) pH 7.4. Membrane homogenat

10、es are incubated for 180 minat room temperature with 50 pM 125I -hCGRP and increasing concentrations of Olcegepant (BIBN4096BS).The incubation is terminated by filtration through GF/B glass fibre filters using a cell harvester. The protein-bound radioactivity is determined in a gamma counter. The no

11、nspecific binding is defined as radioactivitybound in the presence of 1 M CGRP. The IC50 values are obtained by non-linear regression analysis on thebasis of a one binding site model 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 3 Cells a

12、re washed with phosphate-buffered saline then pre-incubated with 300 M isobutylmethylxanthine in2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEserum-free MEM for 30 min at 37 C -CGRP-(S-37) or Olcegepant (BIBN4096BS) is added and the cells areincubated for 10 min before the addition of CGRP. The i

13、ncubation is continued for another 15 min, then thecells are washed with PBS and processed for cAMP determination. Maximal stimulation over basal is definedby using 100 nM CGRP. Doseresponse curves are generated by using Prism 3.MCE has not independently confirmed the accuracy of these methods. They

14、 are for reference only.Animal Rats are treated acutely with Olcegepant (0.3, 0.6, and 0.9 mg/kg, intravenously i.v. in a tail vein),Administration 5 Naratriptan (0.1 and 0.3 mg/kg subcutaneously s.c.), or their respective vehicle. For combined treatment,Olcegepant (0.3 mg/kg, i.v.) is administered

15、30 minutes before Naratriptan (0.1 mg/kg, s.c.). The doses androutes of administration are based on previous reports.For subchronic treatment, CCI-ION and sham-operated rats are injected twice per day for 4 days (at 10 amand 6 pm) with Olcegepant (0.6 mg/kg, i.v.) or its vehicle, starting on the 15t

16、h day after ligature. A furtherinjection of Olcegepant (0.6 mg/kg, i.v.) or vehicle is performed at 10 am the subsequent day (19th day afterligature), just before von Frey filament testing.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nat

17、Med. 2016 Oct;22(10):1160-1169. J Invest Dermatol. 2019 Mar;139(3):656-664. Cell Physiol Biochem. 2017;41(4):1457-1467. Cephalalgia. 2019 Jul 9:333102419861726. Sci Rep. 2018 Jan 30;8(1):1836.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Rudolf K, et al. Development of human

18、calcitonin gene-related peptide (CGRP) receptor antagonists. 1. Potent and selective smallmolecule CGRP antagonists. 1-N2-3,5-dibromo-N-4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinylcarbonyl-D-tyrosyl-l-lysyl-4-(4-pyridinyl)piperazine: the first CGRP antagonist for clinical trials in acute m

19、igraine. J Med Chem. 2005 Sep 22;48(19):5921-31.2. Doods H, et al. Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol. 2000Feb;129(3):420-3.3. Edvinsson L, et al. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omentalarteries and in SK-N-MC cells. Eur J Pharma